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Abstract 4669 Two similarly designed prospective, uncontrolled, open-label clinical trials were planned to assess the safety and efficacy of a new intravenous immunoglobulin (IVIG), IGIV3I 10% Grifols, in subjects with chronic immune thrombocytopenia (ITP) in the USA, Canada and Europe (Spain, Russia and the United Kingdom). Subjects were candidates to be enrolled if they had a diagnosis of chronic ITP and a baseline platelet count ≤ 20 × 109/l. Eligible subjects received treatment with IGIV3I 10% Grifols 1g/kg for 2 consecutive days or 0.4 g/kg for 5 consecutive days. The primary efficacy endpoint was the response rate, defined as the proportion of subjects reaching or exceeding the threshold value of 50 × 109/l on or before day 8 (American study) or on day 30 (European study) where day 1 is the day of the first infusion. Secondary efficacy endpoints were the time to response, defined as the number of days elapsed from day 1 to achievement of the threshold value; duration of response, defined as the number of consecutive days with a platelet count known to be ≥50 × 109/l; the maximum (peak) platelet count and regression of haemorrhagic diathesis for those subjects presenting with bleeding signs at baseline. Safety endpoints included adverse events (AEs), physical examinations, vital signs and clinical laboratory parameters monitoring. A total of 27 subjects (18 adults and 9 pediatrics) have been enrolled, i.e. administered with at least one infusion of the product at any dose, in the study. Twenty-four (24) subjects (89%) were considered responders. This proportion was higher in pediatric subjects (9/9, 100%) than in adult subjects (15/18, 83%). The mean time to response was 1.6 days (Standard Deviation (SD) 0.9); the mean duration of response was 14.0 days (SD 12.1) and the mean maximum platelet count was 263 × 109/l (SD 195.6). Twenty-three (23) subjects (all the pediatric subjects 9/9 and 14/18 adults) presented with some sign of bleeding at baseline. All subjects (23/23, 100%) experienced an improvement in the haemorrhagic diathesis, regardless of some of them being considered non-responders according to the platelet count criterion. A total of 92 AEs potentially related to study drug were reported. The most common of these were headache (25 events), nausea (8 events), pyrexia (7 events) and chills (6 events). Only 1 AE was reported as definitely related to study drug, an event of palmar erythema. Two serious AEs (SAE) potentially related to the study drug were reported in 2 subjects. One of them was an unexpected laboratory alteration which consisted in leukopenia and decreased hemoglobin and advised to maintain the subject hospitalized for further observation during the weekend. The reaction was transient, without complications or other clinical symptoms and total recovery of the normal laboratory values. The second SAE was an event of thrombosis in the right humeral vein, in a patient with a number of predisposing medical conditions. At the time of discharge the patient's overall condition was satisfactory. Analysis of AEs, clinical laboratory values, physical assessments and vital signs did not indicate any safety concerns for subjects receiving the study drug and are in line with those expected for the ITP population treated with IVIG. Both primary and secondary efficacy endpoints show a good response to the product in terms of rapid elevation of platelet counts to an hemostatic level in line with what is expected for an IVIG product. Moreover, the improvement of the baseline bleeding diathesis even in patients considered as non-responders according to the platelet count criterion is highly suggestive of the clinical efficacy of the product. Overall, these results indicate that treatment with the new IGIV3I 10% Grifols is safe and efficacious for rapidly increasing platelet counts in chronic ITP subjects and improving their bleeding diathesis. Disclosures: Khojasteh: Grifols S.A.: Research Funding. Kato:Grifols S.A.: Research Funding. Parikh:Grifols S.A.: Research Funding. Singleton:Grifols S.A.: Research Funding. Tebbi:Grifols S.A.: Research Funding. Cromwell:Grifols S.A.: Research Funding. Fu:Grifols S.A.: Research Funding. Kessler:Grifols S.A.: Research Funding. Letzer:Grifols S.A.: Research Funding. Ritchie:Grifols S.A.: Research Funding. Sexauer:Grifols S.A.: Research Funding. Saxena:Grifols S.A.: Research Funding. Sirpal:Grifols S.A.: Research Funding. Torres:Grifols S.A.: Research Funding. Loriya:Grifols S.A.: Research Funding. Kovaleva:Grifols S.A.: Research Funding. Sandoval:Grifols S.A.: Research Funding. Sanz:Grifols S.A.: Research Funding. Julià:Grifols S.A.: Research Funding. Montañés:Grifols S.A.: Employment. Navarro:Grifols S.A.: Employment.

Idiopathic thrombocytopenic purpura (ITP) is a disease caused by inadequate platelet production as well as increased platelet destruction. Eltrombopag is a first-in-class, oral, non-peptide platelet growth factor that increases platelet counts by interacting with the thrombopoietin receptor on megakaryocytes and their precursors. Accordingly, in two completed 6-week, randomized, double-blind, placebo-controlled studies of adult subjects with chronic ITP, eltrombopag produced a substantial dose-dependent increase in platelet counts. EXTEND is an ongoing, open-label extension study designed to assess the long-term safety and efficacy of oral eltrombopag. Subjects previously enrolled in an eltrombopag study are eligible to enroll in EXTEND after an intervening washout period of at least 4 weeks. Subjects are administered a starting dose of 50 mg/day (which could be increased to 75 mg/day at any time after 3 weeks) in order to reach a platelet count of ≥50,000/uL (stage 1). Then, concomitant ITP medications, if taken at study entry, are tapered to a minimal dose or discontinued entirely (stage 2), whilst maintaining a platelet count of ≥50,000/uL. Eltrombopag is then titrated to a minimal effective dose (25–75 mg/day) required to maintain platelet counts of 50,000/uL-200,000/uL (stage 3). Eltrombopag is continued for as long as the subject continues to benefit (stage 4). Bleeding incidence and severity is assessed using the WHO bleeding scale (Grade 0–4). As of August 6, 2007, data were available on 96 subjects. Ninety-four subjects were administered eltrombopag. Evaluable subjects (n=89) had a median treatment duration of 151 days (2–333 days). At baseline, 42 (44%) subjects had a platelet count ≤15,000/uL, 60 (63%) had evidence of bleeding (WHO Grade 1-4), 44 (46%) were splenectomized, and 35 (36%) were receiving concomitant ITP treatment. Of the sixty-one subjects who entered into the study with a platelet count Stage Description Subjects entering Median Platelet counts (/uL) WHO Grade 2–4 Bleeding n (%) Stage 1 eltrombopag administered 94 16,000 25 (27%) Stage 2 tapering ITP con meds 17 143,500 4 (24%) Stage 3 titrating eltrombpag to maintain platelet counts 46 108,500 3 (7%) Stage 4 treating with eltrombopag long-term 27 104,000 1 (4%)

Background Intravenous immunoglobulin (IVIG) is an accepted treatment for immune thrombocytopenic purpura (ITP). A new liquid 10% human IgG preparation stabilized with proline at a pH of 4.8 (trade name: Privigen) was recently developed. It can be stored at room temperature and is therefore always ready to use. Here we report its efficacy and safety in patients with chronic ITP. Patients and Methods Fifty-seven patients with chronic ITP and a platelet count below 20 x 109/L were included in this open-label, single arm, multi-center Phase III trial. IVIG was given at a dose of 1 g/kg on 2 consecutive days at a maximum infusion rate of 4 mg/kg/min. A subset (56.1%) of the patients received premedication (acetaminophen or diphenhydramine) to avoid adverse events. The primary endpoint was the platelet response rate, defined as the percentage of patients showing an increase in platelet count to ≥50 x 109/L within 7 days of the first infusion. Secondary endpoints included platelet counts at specified time points, time to platelet response, duration of platelet response, and regression of hemorrhages at different bleeding sites. Safety was evaluated by the frequency and severity of adverse events. Results The primary endpoint, an increase in platelet counts to ≥50 x 109/L, was achieved by 81% of the subjects (95% CI: 69–89%). The highest median platelet count (149 x 109/L) was observed on day 8. Median time to response was 2.5 days, with 43% of subjects responding within 1 day. Median duration of platelet response (days with platelet count ≥ 50 x 109/L) was 15.4 days. Regression rates for various bleeding sites ranged from 78% to 100%. Regression of bleeding correlated with increases in platelet counts. Adverse events were reported in 52 (91%) subjects. The most common adverse event was headache (67%), the incidence and severity of which was attenuated by premedication with acetaminophen/diphenhydramine. There were 3 serious adverse events, one of which (aseptic meningitis) was considered related to the study medication. Conclusions The present study has shown the safety and significant efficacy of a novel, 10% liquid, ready for use IVIG preparation, in patients with chronic ITP. A rapid increase in platelet counts to a level where severe bleeding episodes become more unlikely was seen in the majority of patients, as expected with IVIG given at 1 g/kg on 2 consecutive days. The increase in platelet counts was associated with a regression of bleeding. Adverse events were generally mild to moderate in severity, corresponded to those expected with IVIG, and could be prevented with premedication.

Intravenous immunoglobulin (IVIG) products are considered a useful treatment in patients with chronic idiopathic/immune thrombocytopenic purpura (ITP) to prevent bleeding or prior to surgery, when platelet counts have to be rapidly increased. IGIV3I Grifols is a highly purified, unmodified human IgG product whose manufacturing process follows the same basic principles of Flebogamma® (another IVIG manufactured by Grifols in clinical use since 1992). The main differences between both processes are how purification steps are sequentially arranged, and the introduction of two specific steps to inactivate/remove any potential contaminating pathogen (solvent-detergent treatment and sequential nanofiltration through 35 and 20 nm pore size filters), as additional viral elimination steps to pasteurization, already present in Flebogamma®. An open prospective study was planned to investigate the efficacy and safety of IGIV3I Grifols in 20 adult patients with chronic ITP (at least 6 months after diagnosis). Twenty adult subjects were enrolled and 19 patients with chronic ITP in acute phase (platelet counts

Thrombocytopenia in ITP is due to both increased platelet clearance and inadequate platelet production. Bleeding episodes may occur as a result of the thrombocytopenia. Increasing the platelet count in patients with ITP may prevent or decrease bleeding episodes. Eltrombopag is an oral thrombopoietin receptor agonist that stimulates proliferation and differentiation of megakaryocytes and progenitor cells, ultimately increasing the number of circulating platelets. The safety and efficacy of eltrombopag were evaluated in an international, randomized, double-blind, placebo-controlled, phase II trial in adults with chronic, previously-treated ITP and platelets

Introduction Intravenous anti-Rh0(D) immune globulin (anti-D) is used as a platelet enhancing therapy in patients with ITP. The following study was designed to assess the efficacy, tolerability and safety of a new, liquid anti-D (ZLB Behring). Methods This multicenter study was an open-label, single arm, phase III trial of 98 Rh0(D)-positive patients with chronic ITP and a platelet count < 30x109/L. Exclusion criteria included previous splenectomy, HIV infection, pregnancy, anemia (hemoglobin < 100 g/L), and positive Coombs test. The study medication was a chromatographically purified, solvent detergent treated and nanofiltered (15 nm) anti-D. This manufacturing process results in a product with a high purity (particularly a very low IgA content) and an excellent viral safety. Anti-D was provided in pre-filled, ready-to-use syringes and administered at a dose of 50 μg/kg body weight as a single intravenous injection. The primary endpoint was the response rate, defined by the percentage of patients reaching an increase of their platelet count by at least 20x109/L to at least 30x109/L within 15 days. Secondary endpoints included time to platelet response, duration of response and the regression of hemorrhages. For the safety evaluation, blood hemoglobin, serum creatinine and bilirubin levels were closely monitored, in addition to the recording of all adverse events (AE). Results The overall response rate was 66 % (95 % CI: 57 to 75 %). The median time to response was 3 days and the median duration of response was 22 days. A regression of hemorrhages was seen in 88 % of the 50 patients having bleeding at baseline. The most frequent drug related AEs were chills, pyrexia, increase in bilirubin levels and headache. They were generally mild or moderate. A slight decrease in hemoglobin levels (median: -8 g/L) and a slight, transient elevation of bilirubin (median: +0.6 mg/dL) were seen in most patients as expected due the mode of action of anti-D. Clinically relevant elevations in serum creatinine level did not occur (median change: < 0.02 mg/dL). Discussion The present study has demonstrated that the tested anti-D is safe and efficacious in chronic ITP. Response rate, time to response and duration of response were similar to those reported for other platelet enhancing treatments, including high dose corticosteroids, IVIG and other anti-D products. The increase in platelet count was accompanied by a substantial regression of hemorrhages. Drug related adverse events were mainly mild and expected and no cases of severe hemolysis or deterioration of renal function occurred. The liquid, ready-to-use anti-D is an attractive treatment alternative in ITP, offering the convenience of a fast and easy administration.